Exploring Hypertension: The Role of AT1 Receptors, Sartans, and Lipid Bilayers

IF 3.7 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY ACS Omega Pub Date : 2024-11-01 DOI:10.1021/acsomega.4c0635110.1021/acsomega.4c06351
Nikitas Georgiou, Eleni Chontzopoulou, Efthymios Alexandros Routsi, Irene Georgia Stavrakaki, Errikos Petsas, Nikoletta Zoupanou, Margarita Georgia Kakava, Demeter Tzeli, Thomas Mavromoustakos and Sofia Kiriakidi*, 
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Abstract

The rational design of AT1 receptor antagonists represents a pivotal approach in the development of therapeutic agents targeting cardiovascular pathophysiology. Sartans, a class of compounds engineered to inhibit the binding and activation of Angiotensin II on the AT1 receptor, have demonstrated significant clinical efficacy. This review explores the multifaceted role of sartans in mitigating hypertension and related complications. We highlight the integration of crystallography, computational simulations, and NMR spectroscopy to elucidate sartan-AT1 receptor interactions, providing a foundation for the next-generation antagonist design. The review also delves into the challenges posed by the high lipophilicity and suboptimal bioavailability of sartans, emphasizing advancements in nanotechnology and novel drug delivery systems. Additionally, we discuss the impact of lipid bilayers on the AT1 receptor conformation and drug binding, underscoring the importance of the lipidic environment in receptor-drug interactions. We suggest that optimizing drug design to account for these factors could enhance the therapeutic potential of AT1 receptor antagonists, paving the way for improved cardiovascular health outcomes.

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探索高血压:AT1 受体、沙坦类药物和脂质双层膜的作用
合理设计 AT1 受体拮抗剂是开发针对心血管病理生理的治疗药物的关键方法。沙坦类药物是一类抑制血管紧张素 II 与 AT1 受体结合和激活的化合物,已显示出显著的临床疗效。本综述探讨了沙坦类药物在缓解高血压及相关并发症方面的多方面作用。我们重点介绍了结晶学、计算模拟和核磁共振光谱学在阐明沙坦类药物与 AT1 受体相互作用方面的整合,为下一代拮抗剂的设计奠定了基础。综述还深入探讨了沙坦类药物的高亲脂性和不理想的生物利用度所带来的挑战,强调了纳米技术和新型给药系统的进步。此外,我们还讨论了脂质双分子层对 AT1 受体构象和药物结合的影响,强调了脂质环境在受体与药物相互作用中的重要性。我们认为,根据这些因素优化药物设计可以提高 AT1 受体拮抗剂的治疗潜力,为改善心血管健康状况铺平道路。
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来源期刊
ACS Omega
ACS Omega Chemical Engineering-General Chemical Engineering
CiteScore
6.60
自引率
4.90%
发文量
3945
审稿时长
2.4 months
期刊介绍: ACS Omega is an open-access global publication for scientific articles that describe new findings in chemistry and interfacing areas of science, without any perceived evaluation of immediate impact.
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